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Both late-adolescent BMI and ESR are related to mid-life colorectal cancer in a graded fashion.

Body mass index (BMI) as well as inflammation as reflected by the erythrocyte sedimentation rate (ESR) in late adolescence appear to be independently associated with mild-life colorectal cancer (CRC), a Swedish study indicates.

Compared with men who had a normal BMI of 18.5 to < 25 kg/m2 at the age of 16 to 20, men who were overweight with upper BMI of between 27.5 to < 30 kg/m2 at the same point in time had a 2.08-fold higher risk of CRC (95% CI 1.40-30.907) at an average follow-up some 35 years later.

Late adolescent males who were obese with a BMI of 30 kg/m2 or greater had a 2.38-fold higher risk of CRC (95% CI 1.51-3.76); P<0.001) at the same follow-up point in mid-life.

Similarly, male adolescents with the highest ESR of ≥15 mm/h had a 63% higher risk of CRC 35 years later (Hazard Ratio (HR): 1.63; 95% CI 1.09-2.45) than those with a low ESR <10 mm/h (P=0.006).

ESR is a nonspecific marker of inflammation and rises and falls slowly, making it suitable for tracking inflammation among patients with chronic conditions.

"In this cohort of Swedish men, late-adolescent BMI and inflammation, as measured by ESR, were associated with risk of subsequent CRC, suggesting that BMI and inflammation in adolescence may play a role in the development of CRC," Elizabeth Kantor, PhD, Harvard School of Public Health, and colleagues write in Gut.

"The BMI-CRC association (evident for both upper overweight and obese adolescents) was independent of ESR, indicating that adolescent BMI may affect CRC risk through mechanisms other than inflammation, as measured by ESR."

The study population of 239,658 subjects was drawn from a cohort of Swedish males who underwent a compulsory conscription assessment between 1969 and 1976, during which time, conscription was mandatory for male Swedish citizens.

Conscription took place in late adolescence, at a mean age of 18.5 years.

Prior to conscription, men completed extensive physical and psychological examinations and BMI as well as ESR values were recorded.

Nearly 12% of the study population were underweight at a BMI of <18 kg/m2 while 81% were normal weight with a BMI from 18.5 to < 25 kg/m2.

Only 5% of the overall cohort had a BMI that fell into the lower overweight group (BMI 25 to < 27/5 kg/m2 while 1.5% had a BMI that fell into the upper overweight group (BMI 27.5 to < 30 kg/m2).

Fewer than 1% were obese with a BMI > 30 kg/m2.

Over 96% of men in the cohort had a normal ESR at the time of conscription while 2% had a moderate ESR and 1.7% a high ESR.

Over an average of 35 years of follow-up, 885 diagnoses of CRC occurred including 501 diagnoses of colon cancer and 384 diagnoses of rectal cancer.

Again in full multivariable adjustment, a moderate ESR of between 10 and < 15 was associated with a nonsignificant 40% increased risk of CRC compared with normal ESR < 10 (HR: 1.40; 95% CI 0.93-2.10)

As the authors point out, men in the study were followed on average for 35 years but they were not followed into late adulthood as the average age at the end of follow-up was 53.9 years.

"Thus, the etiology of the early-to-mid-life CRC diagnoses may differ from those occurring later in adulthood," researchers observe.

"In fact, the strong association observed between adolescent obesity and early-to-mid-life CRC, coupled with the increasing prevalence of adolescent obesity, may shed light on the increase in CRC incidence among young adults in the USA," they add.

The study is the first to report on the association between adolescence inflammation and CRC risk so it cannot be compared with other studies.

However, there is a "vast literature" on adult inflammation and CRC, all of which suggests a positive association between inflammation and CRC.

"The putative role of inflammation in colorectal carcinogenesis is further corroborated by the fact that aspirin, an anti-inflammatory, has been shown to reduce CRC risk and mortality," the authors state.

At the same time, they caution that study-specific conclusions regarding ESR may not be generalizable to other markers of inflammation.

The authors also made an effort to exclude men known to be diagnosed with inflammatory bowel disease (IBD) before conscription and performed a sensitivity analysis to further exclude those seeking inpatient care for IBD in the first 10 years of follow-up.

Sensitivity analysis did attenuate the association between high ESR and CRC risk but even if some of the association is accounted for by subclinical IBD at conscription, "it does not appear to account for the entirety of the association," they state.

Investigators also point out that they were unable to comment on whether the strong association between adolescent BMI and CRC could be mitigated by weight loss during adulthood.

BMI and inflammation in adolescence are likely associated with exposure in both childhood and adulthood as they note, and it is plausible that it is the total duration of exposure to higher BMI or high levels of inflammation that confers the observed increased risk for CRC rather than exposure at a specific period of life.

BMI may also not be the ideal measure of adiposity in this period of growth between 16 and 20 years of age.

"It is important that we understand the role of exposures in childhood and adolescence in the development of CRC, both to enhance our understanding of the aetiology of this disease and to shed light on potential points of intervention," the authors observe.

"And results suggest that BMI and inflammation, as measured by ESR, in early life may be important to the development of CRC."

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